30 Years On-The Human Genome Project Impact, What the Future Portends

Wired 12.30.2020 07:00 AM |SCIENCE| “30 Years Since the Human Genome Project Began, What’s Next? “Eric Green, head of the nation’s top genomics research institute, looks back on how far the field has come and shares his bold vision for the future.” By Megan Molteni.

Image from 2020 NHGRI Short Course in Genomics. About one hour on YouTube.com

Read the full article for all details of the interview.

Summary of Article

National Human Genomics Institute (NHGRI) founded in 1989 by an action of Congress.

Sequencing of the human genome began in 1990 and was completed in 2003.

Shortly after Eric “green took the helm”…of NHGRI the “mission had evolved to include expanding the field of genomics into medicine” in a effort “aimed at pinpointing the mutations responsible for genetic disorders, then developing tests to diagnose them and therapies to treat them.” NHGRI laid out its latest “projection in October”…including “a set of 10 bold predictions…” that might be realized by 2030. Highlights include “High schoolers”…showing off “genetic analyses at the science fair, and [that] genomic testing at the doctor’s office will become as routine as basic blood work.”

Q: [Partial] “When you look around at where we are today, how does it live up to the expectations you had for impacts the project would make in medicine?”

A: [All A: will be paraphrased with some direct quotes]. Early on we “didn’t know what we were doing.” We had a big goal “but we didn’t have the technology to do it.” “There was no playbook.” Genomics in medicine “I truly did not think it would happen in my lifetime.” Just in the last ten years that we began “using genomics in health care.” “That was a hypothetical in 2011, Now it’s routine. At least for people suspected of having a rare genetic disease.”

Q: [Partial] “in 2000, then NHGRI director Francis Collins” was quoted as saying “it would likely take 15 or 20 years to see a ‘complete transformation in therapeutic medicine’.”…” Obviously, that hasn’t come to pass. Why not?”

A: Sequencing is available with a going rate of $1,000 but “for a generally healthy person, we wouldn’t know what to do with the information.” “That’s why I haven’t had my genome sequenced yet.”

Q: “You haven’t”

A: No…”there’s this massive gap between having the data…and knowing what it all means.” We must know the biological function “of every human gene.” …”progress is likely going to be measured more in decades than in years.”

Q: “Are there any emerging technologies you can point to that are accelerating progress toward closing that gap?”

A: Crispr “this year’s Nobel Prize” has beyond treatments recently highlighted has a “far bigger use is at the bench. With Crisper, we can make edits to little pieces of DNA” in bacteria and laboratory cultured cell lines and then “see if those edits have functional consequences.” …”genome editing”, “genome synthesis methods” are getting better “coupled with better…computational tools”…this promises to “change the pace of biological discovery.” Our current method of publishing one “genomic variant” at a time”…”doesn’t scale.” The idea now is “making millions of changes, generating massive amounts of data, and then hopefully we can use AI to train computers to look for patterns.”

Q: [Partial] …”sounds like a big lift”

A: Big advances in technology but the bottleneck now is dealing with “all that data.” Eric Green comments that the greatest needs is having “a single institute leading in data science. Right now, we don’t have one.”

Q: [Partial] “What other barriers” for the next decade”

A: “not all insurance companies are willing to pay for a genome sequence. That’s a problem for people with undiagnosed rare diseases. We’ve had much better success in the cancer world, where genetic testing has really gone mainstream, and in prenatal testing.”

Q:”How is NHGRI proposing to tackle those challenges?”

A: “…It’s complicated.” …”We’re…unveiling an action agenda for creating a more diverse workforce in genomics”…idea being “If the workforce is more diverse, then genomics will be more uniformly taken up in medicine…”. Along those same lines on the basic science level current reference genomes are mostly comprised of European-ancestry and going forward “the goal…is a “pan-genome”…to always have available an appropriately matched data set available for medical interpretation.”

Q: [Partial]. “What corners [of medical care] are “the hardest to reach?”

A: “The hardest category is going to be preventing common diseases-hypertension, diabetes, cardiovascular disease, asthma, autism, Alzheimer’s etc. We’re starting to develop polygenic risk scores for these, but we still don’t know how truly predictive they’re going to be.”

Q: [Partial] “What about genomics and infectious disease?”

A: …”rarely [is there] a problem in biomedicine these days where genomics isn’t somewhere in there playing a role.” … “If you follow the timeline of this pandemic, the first report of the virus was late December. Within two weeks of that, the sequence of the virus was released publicly.” … a legacy of the Human Genome project…is that from then on [2003] “it changed forever the way scientists shared genetic data.”

Q: [Partial] Having that COVID sequence being available so quickly “was a real win for public health”

A: “Yes! That sequence was instantly used to make tests…and it was step one for developing vaccines.” The Human Genome project “wasn’t a traditional science project. We were creating a community resource…its “One of its most lasting legacies is the way it really transformed the rules of research.”